Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1.

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.

Programa intercultural pel Centre Penitenciari de Figures: activitat per treballar la interculturalitat amb interns del Centre Penitenciari de Figueres

Proposta d’activitat per treballar la interculturalitat en el centre penitenciari de Figueres des del punt de vista de l’educador social. L’activitat consisteix en la creació i manteniment d’un blog obert a tots els interns mitjançant la xarxa moodle. L’autora aprofita per fer una extensa contextualització de la realitat del CP de Figueres

The TRANSMED Atlas: geological-geophysical fabric of the Mediterranean region - Final report of the project

Geological research on the Mediterranean region is presently characterized by the transition from disciplinary to multidisciplinary research, as well as from national to international investigations. In order to synthesize and integrate the vast disciplinary and national datasets which are available, it is necessary to implement maximum interaction among geoscientists of different backgrounds. The creation of project-oriented task forces in universities and other research institutions, as well as the development of large international cooperation programs, is instrumental in pursuing such a multidisciplinary and supranational approach. The TRANSMED Atlas, an official publication of the 32nd International Geological Congress (Florence 2004), is the result of an international scientific cooperation program which brought together for over two years sixty-three structural geologists, geophysicists, marine geologists, petrologists, sedimentologists, stratigraphers, paleogeographers, and petroleum geologists coming from eighteen countries, and working for the petroleum industry, academia, and other institutions, both public and private. The TRANSMED Atlas provides an updated, synthetic, and coherent portrayal of the overall geological-geophysical structure of the Mediterranean domain and the surrounding areas. The initial stimulus for the Atlas came from the realization of the extremely heterogeneous nature of the existing geological-geophysical data about such domain. These data have been gathered by universities, oil companies, geological surveys and other institutions in several countries, often using different procedures and standards. In addition, much of these data are written in languages and published in outlets that are not readily accessible to the general international reader. By synthesizing and integrating a wealth of preexisting and new data derived from surficial geology, seismic sections at various scales, and mantle tomographies, the TRANSMED Atlas provides for the first time a coherent geological overview of the Mediterranean region and represents an ideal springboard for future studies.

Database resources for the tuberculosis community.

Access to online repositories for genomic and associated "-omics" datasets is now an essential part of everyday research activity. It is important therefore that the Tuberculosis community is aware of the databases and tools available to them online, as well as for the database hosts to know what the needs of the research community are. One of the goals of the Tuberculosis Annotation Jamboree, held in Washington DC on March 7th-8th 2012, was therefore to provide an overview of the current status of three key Tuberculosis resources, TubercuList (tuberculist.epfl.ch), TB Database (www.tbdb.org), and Pathosystems Resource Integration Center (PATRIC, www.patricbrc.org). Here we summarize some key updates and upcoming features in TubercuList, and provide an overview of the PATRIC site and its online tools for pathogen RNA-Seq analysis.

Evidence for an episodic model of protein sequence evolution.

The evolution of protein function appears to involve alternating periods of conservative evolution and of relatively rapid change. Evidence for such episodic evolution, consistent with some theoretical expectations, comes from the application of increasingly sophisticated models of evolution to large sequence datasets. We present here some of the recent methods to detect functional shifts, using amino acid or codon models. Both provide evidence for punctual shifts in patterns of amino acid conservation, including the fixation of key changes by positive selection. Although a link to gene duplication, a presumed source of functional changes, has been difficult to establish, this episodic model appears to apply to a wide variety of proteins and organisms.

Topographic ERP analyses: a step-by-step tutorial review.

In this tutorial review, we detail both the rationale for as well as the implementation of a set of analyses of surface-recorded event-related potentials (ERPs) that uses the reference-free spatial (i.e. topographic) information available from high-density electrode montages to render statistical information concerning modulations in response strength, latency, and topography both between and within experimental conditions. In these and other ways these topographic analysis methods allow the experimenter to glean additional information and neurophysiologic interpretability beyond what is available from canonical waveform analyses. In this tutorial we present the example of somatosensory evoked potentials (SEPs) in response to stimulation of each hand to illustrate these points. For each step of these analyses, we provide the reader with both a conceptual and mathematical description of how the analysis is carried out, what it yields, and how to interpret its statistical outcome. We show that these topographic analysis methods are intuitive and easy-to-use approaches that can remove much of the guesswork often confronting ERP researchers and also assist in identifying the information contained within high-density ERP datasets.

Metabolomics in the fight against malaria

Metabolomics uses high-resolution mass spectrometry to provide a chemical fingerprint of thousands of metabolites present in cells, tissues or body fluids. Such metabolic phenotyping has been successfully used to study various biologic processes and disease states. High-resolution metabolomics can shed new light on the intricacies of host-parasite interactions in each stage of the Plasmodium life cycle and the downstream ramifications on the host’s metabolism, pathogenesis and disease. Such data can become integrated with other large datasets generated using top-down systems biology approaches and be utilised by computational biologists to develop and enhance models of malaria pathogenesis relevant for identifying new drug targets or intervention strategies. Here, we focus on the promise of metabolomics to complement systems biology approaches in the quest for novel interventions in the fight against malaria. We introduce the Malaria Host-Pathogen Interaction Center (MaHPIC), a new systems biology research coalition. A primary goal of the MaHPIC is to generate systems biology datasets relating to human and non-human primate (NHP) malaria parasites and their hosts making these openly available from an online relational database. Metabolomic data from NHP infections and clinical malaria infections from around the world will comprise a unique global resource.

Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.

BACKGROUND: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profiles of breast cancers and whether such profiles could be used to improve histologic grading. METHODS: We analyzed microarray data from 189 invasive breast carcinomas and from three published gene expression datasets from breast carcinomas. We identified differentially expressed genes in a training set of 64 estrogen receptor (ER)-positive tumor samples by comparing expression profiles between histologic grade 3 tumors and histologic grade 1 tumors and used the expression of these genes to define the gene expression grade index. Data from 597 independent tumors were used to evaluate the association between relapse-free survival and the gene expression grade index in a Kaplan-Meier analysis. All statistical tests were two-sided. RESULTS: We identified 97 genes in our training set that were associated with histologic grade; most of these genes were involved in cell cycle regulation and proliferation. In validation datasets, the gene expression grade index was strongly associated with histologic grade 1 and 3 status; however, among histologic grade 2 tumors, the index spanned the values for histologic grade 1-3 tumors. Among patients with histologic grade 2 tumors, a high gene expression grade index was associated with a higher risk of recurrence than a low gene expression grade index (hazard ratio = 3.61, 95% confidence interval = 2.25 to 5.78; P < .001, log-rank test). CONCLUSIONS: Gene expression grade index appeared to reclassify patients with histologic grade 2 tumors into two groups with high versus low risks of recurrence. This approach may improve the accuracy of tumor grading and thus its prognostic value.

Aproximación a la comunidad artista amateur japonesa

En este trabajo se analiza el modelo de profesionalización del colectivo de artistas amateurs propuesto desde el soporte de las comunidades online, con sede en Japón, Pixiv, Drawr y Tegaki Blog. Partiendo tanto del análisis de la propia actividad online por medio de la observación participante, como del análisis iconográfico e iconológico de las publicaciones derivadas de dichas comunidades, se intentará determinar aquella estética que resulta favorecida con fines comerciales y que propicia el salto al mundo profesional. También se abordará la influencia del manga (cómic japonés) y del movimiento artístico conocido como Superflat en la institucionalización de dicha estética

Los blogs: comparativa de tres casos prácticos

El present treball de final de carrera reflexiona sobre la importància que tenen els blocs actualment i analitza i compara tres casos pràctics per a obtenir un resultat que, posteriorment, tractarem d’aplicar al nostre bloc personal: Diezcontraonce. Des de l’aparició dels blocs, les empreses confien cada vegada més en aquesta eina per a comunicar els seus missatges. Alguns blogaires han adquirit un gran nivell d’influència i les empreses els tenen en compte, tant o més que als mitjans de comunicació. Casos com Enrique Dans, TcBlog i El Blog de Juan Merodio ens ajudaran a convertir el nostre blog en una potent eina de comunicació, influent i amb èxit. I ara, seran capaços els blogs i els blocaires de desbancar del tot als tradicionals mitjans de comunicació?

Bayesian tools for zero counts in compositional data

The log-ratio methodology makes available powerful tools for analyzing compositionaldata. Nevertheless, the use of this methodology is only possible for those data setswithout null values. Consequently, in those data sets where the zeros are present, aprevious treatment becomes necessary. Last advances in the treatment of compositionalzeros have been centered especially in the zeros of structural nature and in the roundedzeros. These tools do not contemplate the particular case of count compositional datasets with null values. In this work we deal with \count zeros" and we introduce atreatment based on a mixed Bayesian-multiplicative estimation. We use the Dirichletprobability distribution as a prior and we estimate the posterior probabilities. Then weapply a multiplicative modi¯cation for the non-zero values. We present a case studywhere this new methodology is applied.Key words: count data, multiplicative replacement, composition, log-ratio analysis

CATMA, a comprehensive genome-scale resource for silencing and transcript profiling of Arabidopsis genes.

BACKGROUND: The Complete Arabidopsis Transcript MicroArray (CATMA) initiative combines the efforts of laboratories in eight European countries 1 to deliver gene-specific sequence tags (GSTs) for the Arabidopsis research community. The CATMA initiative offers the power and flexibility to regularly update the GST collection according to evolving knowledge about the gene repertoire. These GST amplicons can easily be reamplified and shared, subsets can be picked at will to print dedicated arrays, and the GSTs can be cloned and used for other functional studies. This ongoing initiative has already produced approximately 24,000 GSTs that have been made publicly available for spotted microarray printing and RNA interference. RESULTS: GSTs from the CATMA version 2 repertoire (CATMAv2, created in 2002) were mapped onto the gene models from two independent Arabidopsis nuclear genome annotation efforts, TIGR5 and PSB-EuGène, to consolidate a list of genes that were targeted by previously designed CATMA tags. A total of 9,027 gene models were not tagged by any amplified CATMAv2 GST, and 2,533 amplified GSTs were no longer predicted to tag an updated gene model. To validate the efficacy of GST mapping criteria and design rules, the predicted and experimentally observed hybridization characteristics associated to GST features were correlated in transcript profiling datasets obtained with the CATMAv2 microarray, confirming the reliability of this platform. To complete the CATMA repertoire, all 9,027 gene models for which no GST had yet been designed were processed with an adjusted version of the Specific Primer and Amplicon Design Software (SPADS). A total of 5,756 novel GSTs were designed and amplified by PCR from genomic DNA. Together with the pre-existing GST collection, this new addition constitutes the CATMAv3 repertoire. It comprises 30,343 unique amplified sequences that tag 24,202 and 23,009 protein-encoding nuclear gene models in the TAIR6 and EuGène genome annotations, respectively. To cover the remaining untagged genes, we identified 543 additional GSTs using less stringent design criteria and designed 990 sequence tags matching multiple members of gene families (Gene Family Tags or GFTs) to cover any remaining untagged genes. These latter 1,533 features constitute the CATMAv4 addition. CONCLUSION: To update the CATMA GST repertoire, we designed 7,289 additional sequence tags, bringing the total number of tagged TAIR6-annotated Arabidopsis nuclear protein-coding genes to 26,173. This resource is used both for the production of spotted microarrays and the large-scale cloning of hairpin RNA silencing vectors. All information about the resulting updated CATMA repertoire is available through the CATMA database http://www.catma.org.

Influence of the LILRA3 Deletion on Multiple Sclerosis Risk: Original Data and Meta-Analysis.

BACKGROUND Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Additional risk loci with immunologically relevant genes were found significantly overrepresented. Nonetheless, it is accepted that most of the genetic architecture underlying susceptibility to the disease remains to be defined. Candidate association studies of the leukocyte immunoglobulin-like receptor LILRA3 gene in MS have been repeatedly reported with inconsistent results. OBJECTIVES In an attempt to shed some light on these controversial findings, a combined analysis was performed including the previously published datasets and three newly genotyped cohorts. Both wild-type and deleted LILRA3 alleles were discriminated in a single-tube PCR amplification and the resulting products were visualized by their different electrophoretic mobilities. RESULTS AND CONCLUSION Overall, this meta-analysis involved 3200 MS patients and 3069 matched healthy controls and it did not evidence significant association of the LILRA3 deletion [carriers of LILRA3 deletion: p = 0.25, OR (95% CI) = 1.07 (0.95-1.19)], even after stratification by gender and the HLA-DRB1*15:01 risk allele.

Application of discriminant function analysis and change-point problem in dating volcanic ashes

The application of Discriminant function analysis (DFA) is not a new idea in the studyof tephrochrology. In this paper, DFA is applied to compositional datasets of twodifferent types of tephras from Mountain Ruapehu in New Zealand and MountainRainier in USA. The canonical variables from the analysis are further investigated witha statistical methodology of change-point problems in order to gain a betterunderstanding of the change in compositional pattern over time. Finally, a special caseof segmented regression has been proposed to model both the time of change and thechange in pattern. This model can be used to estimate the age for the unknown tephrasusing Bayesian statistical calibration